Sickle cell disease in the older adult

Pathology

Volumn 49, Issue 1, 2017, Pages 1-9

  Thein, Mya S ^a   Igbineweka, Norris E ^b   Thein, Swee Lay ^a  

^a NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

^b UNIVERSITY OF SUSSEX   (United Kingdom)

Author keywords

multi organ damage; older adults; Sickle cell disease; vasculopathy

Indexed keywords

HYDROXYUREA;

AGED; BLOOD TRANSFUSION; BONE DISEASE; ELDERLY CARE; HEPATOBILIARY DISEASE; HUMAN; KIDNEY DISEASE; LUNG COMPLICATION; NEUROLOGICAL COMPLICATION; PAIN; PATHOPHYSIOLOGY; REVIEW; SICKLE CELL ANEMIA; VENOUS THROMBOEMBOLISM; AGING; ANEMIA, SICKLE CELL; COMPLICATION; HEALTH CARE DELIVERY; ORGANS AT RISK; PAIN MEASUREMENT; PATHOLOGY; PHYSIOLOGY;

AGING; ANEMIA, SICKLE CELL; DELIVERY OF HEALTH CARE; HUMANS; ORGANS AT RISK; PAIN; PAIN MEASUREMENT;

EID: 85006371096     PISSN: 00313025     EISSN: 14653931     Source Type: Journal    
DOI: 10.1016/j.pathol.2016.10.002     Document Type: Review

References (120)

1. 1 Aygun, B., Odame, I., A global perspective on sickle cell disease. Pediatr Blood Cancer 59 (2012), 386–390.
2. 2 Piel, F.B., Patil, A.P., Howes, R.E., et al. Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates. Lancet 381 (2013), 142–151.
3. 3 Hamideh, D., Alvarez, O., Sickle cell disease related mortality in the United States (1999–2009). Pediatr Blood Cancer 60 (2013), 1482–1486.
4. 4 Platt, O.S., Brambilla, D.J., Rosse, W.F., et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med 330 (1994), 1639–1644.
5. 5 Elmariah, H., Garrett, M.E., De Castro, L.M., et al. Factors associated with survival in a contemporary adult sickle cell disease cohort. Am J Hematol 89 (2014), 530–535.
6. 6 Gardner, K., Douiri, A., Drasar, E., et al. Survival in adults with sickle cell disease in a high-income setting. Blood 128 (2016), 1436–1438.
7. 7 Lanzkron, S., Carroll, C.P., Haywood, C. Jr., Mortality rates and age at death from sickle cell disease: US, 1979–2005. Public Health Rep 128 (2013), 110–116.
8. 8 Powars, D.R., Chan, L.S., Hiti, A., et al. Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine 84 (2005), 363–376.
9. 9 Herrick, J.B., Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. Arch Intern Med 6 (1910), 517–521.
10. 10 Pauling, L., Itano, H.A., Singer, S.J., et al. Sickle cell anemia: a molecular disease. Science 110 (1949), 543–548.
11. 11 Ingram, V.M., Gene mutations in human haemoglobin: the chemical difference between normal and sickle cell haemoglobin. Nature 180 (1957), 326–328.
12. 12 Goldstein, J., Konigsberg, W., Hill, R.J., The structure of human hemoglobin: VI. The sequence of amino acids in the tryptic peptides of the β chain. J Biol Chem 238 (1963), 2016–2027.
13. 13 Neel, J.V., The inheritance of sickle cell anemia. Science 110 (1949), 64–66.
14. 14 Rees, D.C., Williams, T.N., Gladwin, M.T., Sickle-cell disease. Lancet 376 (2010), 2018–2031.
15. 15 Gardner, K., Thein, S.L., Genetic factors modifying sickle cell disease severity. Costa, F.F., Conran, N., (eds.) Sickle Cell Anemia – From Basic Science to Clinical Practice, 2016, Springer International, Switzerland, 371–397.
16. 16 Vasavda, N., Menzel, S., Kondaveeti, S., et al. The linear effects of alpha-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease. Br J Haematol 138 (2007), 263–270.
17. 17 Ballas, S.K., Effect of alpha-globin genotype on the pathophysiology of sickle cell disease. Pediatr Pathol Mol Med 20 (2001), 107–121.
18. 18 Embury, S.H., Dozy, A.M., Miller, J., et al. Concurrent sickle-cell anemia and alpha-thalassemia: effect on severity of anemia. N Engl J Med 306 (1982), 270–274.
19. 19 Embury, S.H., Clark, M.R., Monroy, G., et al. Concurrent sickle cell anemia and alpha-thalassemia. Effect on pathological properties of sickle erythrocytes. J Clin Invest 73 (1984), 116–123.
20. 20 Embury, S.H., Hebbel, R.P., Mohandas, N., et al. (eds.) Sickle Cell Disease: Basic Principles and Clinical Practice, 1994, Raven Press, New York.
21. 21 Day, T.G., Drašar, E.R., Fulford, T., et al. Association between hemolysis and albuminuria in adults with sickle cell anemia. Haematologica 97 (2012), 201–205.
22. 22 Bernaudin, F., Verlhac, S., Chevret, S., et al. G6PD deficiency, absence of alpha-thalassemia, and hemolytic rate at baseline are significant independent risk factors for abnormally high cerebral velocities in patients with sickle cell anemia. Blood 112 (2008), 4314–4317.
23. 23 Flanagan, J.M., Frohlich, D.M., Howard, T.A., et al. Genetic predictors for stroke in children with sickle cell anemia. Blood 117 (2011), 6681–6684.
24. 24 Cox, S.E., Makani, J., Soka, D., et al. Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase polymorphisms and risk of abnormal transcranial Doppler among patients with sickle cell anaemia in Tanzania. Br J Haematol 165 (2014), 699–706.
25. 25 Thein, S.L., Genetic modifiers of sickle cell disease. Hemoglobin 35 (2011), 589–606.
26. 26 Pagnier, J., Mears, J.G., Dunda-Belkhodja, O., et al. Evidence for the multicentric origin of the sickle cell hemogloin gene in Africa. Proc Natl Acad Sci USA 81 (1984), 1771–1773.
27. 27 Nagel, R.L., Rao, S.K., Dunda-Belkhodja, O., et al. The hematologic characteristics of sickle cell anemia bearing the Bantu haplotype: the relationship between G gamma and HbF level. Blood 69 (1987), 1026–1030.
28. 28 Labie, D., Pagnier, J., Lapoumeroulie, C., et al. Common haplotype dependency of high G gamma-globin gene expression and high Hb F levels in beta-thalassemia and sickle cell anemia patients. Proc Natl Acad Sci USA 82 (1985), 2111–2114.
29. 29 Platt, O.S., Thorington, B.D., Brambilla, D.J., et al. Pain in sickle cell disease: rates and risk factors. N Engl J Med 325 (1991), 11–16.
30. 30 Wang, W.C., Pavlakis, S.G., Helton, K.J., et al. MRI abnormalities of the brain in one-year-old children with sickle cell anemia. Pediatr Blood Cancer 51 (2008), 643–646.
31. 31 Thomas, P.W., Higgs, D.R., Serjeant, G.R., Benign clinical course in homozygous sickle cell disease: a search for predictors. J Clin Epidemiol 50 (1997), 121–126.
32. 32 Yawn, B.P., Buchanan, G.R., Afenyi-Annan, A.N., et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA 312 (2014), 1033–1048.
33. 33 Savage, W.J., Buchanan, G.R., Yawn, B.P., et al. Evidence gaps in the management of sickle cell disease: a summary of needed research. Am J Hematol 90 (2015), 273–275.
34. 34 Bunn, H.F., Pathogenesis and treatment of sickle cell disease. N Engl J Med 337 (1997), 762–769.
35. 35 Hebbel, R.P., Osarogiagbon, R., Kaul, D., The endothelial biology of sickle cell disease: inflammation and a chronic vasculopathy. Microcirculation 11 (2004), 129–151.
36. 36 Reiter, C.D., Wang, X., Tanus-Santos, J.E., et al. Cell-free hemoglobin limits nitric oxide bioavailability in sickle cell disease. Nat Med 8 (2002), 1383–1389.
37. 37 Moncada, S., Higgs, E.A., Nitric oxide and the vascular endothelium. Handb Exp Pharmacol 176 (2006), 213–254.
38. 38 McCurdy, P.R., Sherman, A.S., Irreversibly sickled cells and red cell survival in sickle cell anemia: a study with both DF32P and 51CR. Am J Med 64 (1978), 253–258.
39. 39 Kato, G.J., Gladwin, M.T., Steinberg, M.H., Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Rev 21 (2007), 37–47.
40. 40 National Institutes of Health: National Heart Lung and Blood Institute, Evidence-Based Management of Sickle Cell Disease: NIH Expert Panel Report., Vol 161, 2014, US Department of Health and Human Services, Bethesda.
41. 41 Ballas, S.K., Lusardi, M., Hospital readmission for adult acute sickle cell painful episodes: frequency, etiology, and prognostic significance. Am J Hematol 79 (2005), 17–25.
42. 42 Panepinto, J.A., Brousseau, D.C., Hillery, C.A., et al. Variation in hospitalizations and hospital length of stay in children with vaso-occlusive crises in sickle cell disease. Pediatr Blood Cancer 44 (2005), 182–186.
43. 43 Lanzkron, S., Haywood, C. Jr., The five key things you need to know to manage adult patients with sickle cell disease. Hematology Am Soc Hematol Educ Program 2015 (2015), 420–425.
44. 44 Taylor, L.E., Stotts, N.A., Humphreys, J., et al. A review of the literature on the multiple dimensions of chronic pain in adults with sickle cell disease. J Pain Symptom Manage 40 (2010), 416–435.
45. 45 Anie, K.A., Steptoe, A., Bevan, D.H., Sickle cell disease: pain, coping and quality of life in a study of adults in the UK. Br J Health Psychol 7 (2002), 331–344.
46. 46 Ballas, S.K., Barton, F.B., Waclawiw, M.A., et al. Hydroxyurea and sickle cell anemia: effect on quality of life. Health Qual Life Outcomes, 4, 2006, 59.
47. 47 Marti-Carvajal, A.J., Agreda-Perez, L.H., Antibiotics for treating osteomyelitis in people with sickle cell disease. Cochrane Database Syst Rev, 12, 2012, CD007175.
48. 48 Almeida, A., Roberts, I., Bone involvement in sickle cell disease. Br J Haematol 129 (2005), 482–490.
49. 49 Osunkwo, I., An update on the recent literature on sickle cell bone disease. Curr Opin Endocrinol Diabetes Obesity 20 (2013), 539–546.
50. 50 Milner, P.F., Kraus, A.P., Sebes, J.I., et al. Sickle cell disease as a cause of osteonecrosis of the femoral head. N Engl J Med 325 (1991), 1476–1481.
51. 51 Issa, K., Naziri, Q., Maheshwari, A.V., et al. Excellent results and minimal complications of total hip arthroplasty in sickle cell hemoglobinopathy at mid-term follow-up using cementless prosthetic components. J Arthroplasty 28 (2013), 1693–1698.
52. 52 Jack, C.M., Howard, J., Aziz, E.S., et al. Cementless total hip replacements in sickle cell disease. Hip Int 26 (2016), 186–192.
53. 53 Vichinsky, E.P., Styles, L.A., Colangelo, L.H., et al. Acute chest syndrome in sickle cell disease: clinical presentation and course. Cooperative Study of Sickle Cell Disease. Blood 89 (1997), 1787–1792.
54. 54 Castro, O., Brambilla, D.J., Thorington, B., et al. The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease. Blood 84 (1994), 643–649.
55. 55 Vichinsky, E.P., Neumayr, L.D., Earles, A.N., et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group. N Engl J Med 342 (2000), 1855–1865.
56. 56 Dang, N.C., Johnson, C., Eslami-Farsani, M., et al. Bone marrow embolism in sickle cell disease: a review. Am J Hematol 79 (2005), 61–67.
57. 57 Knight-Madden, J.M., Forrester, T.S., Lewis, N.A., et al. The impact of recurrent acute chest syndrome on the lung function of young adults with sickle cell disease. Lung 188 (2010), 499–504.
58. 58 Miller, A.C., Gladwin, M.T., Pulmonary complications of sickle cell disease. Am J Respir Crit Care Med 185 (2012), 1154–1165.
59. 59 De Castro, L.M., Jonassaint, J.C., Graham, F.L., et al. Pulmonary hypertension associated with sickle cell disease: clinical and laboratory endpoints and disease outcomes. Am J Hematol 83 (2008), 19–25.
60. 60 Castro, O., Gladwin, M.T., Pulmonary hypertension in sickle cell disease: mechanisms, diagnosis, and management. Hematol Oncol Clin North Am 19 (2005), 881–896 vii.
61. 61 Sharma, S., Efird, J.T., Knupp, C., et al. Sleep disorders in adult sickle cell patients. J Clin Sleep Med 11 (2015), 219–223.
62. 62 Aldrich, T.K., Dhuper, S.K., Patwa, N.S., et al. Pulmonary entrapment of sickle cells: the role of regional alveolar hypoxia. J Appl Physiol 80 (1996), 531–539.
63. 63 Gladwin, M.T., Sachdev, V., Jison, M.L., et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 350 (2004), 886–895.
64. 64 Parent, F., Bachir, D., Inamo, J., et al. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med 365 (2011), 44–53.
65. 65 Ataga, K.I., Moore, C.G., Jones, S., et al. Pulmonary hypertension in patients with sickle cell disease: a longitudinal study. Br J Haematol 134 (2006), 109–115.
66. 66 Mehari, A., Gladwin, M.T., Tian, X., et al. Mortality in adults with sickle cell disease and pulmonary hypertension. JAMA 307 (2012), 1254–1256.
67. 67 Fonseca, G.H., Souza, R., Salemi, V.M., et al. Pulmonary hypertension diagnosed by right heart catheterisation in sickle cell disease. Eur Respir J 39 (2012), 112–118.
68. 68 Bunn, H.F., Nathan, D.G., Dover, G.J., et al. Pulmonary hypertension and nitric oxide depletion in sickle cell disease. Blood 116 (2010), 687–692.
69. 69 Gladwin, M.T., Vichinsky, E., Pulmonary complications of sickle cell disease. N Engl J Med 359 (2008), 2254–2265.
70. 70 Gordeuk, V.R., Castro, O.L., Machado, R.F., Pathophysiology and treatment of pulmonary hypertension in sickle cell disease. Blood 127 (2016), 820–828.
71. 71 Mushemi-Blake, S., Melikian, N., Drasar, E., et al. Pulmonary haemodynamics in sickle cell disease are driven predominantly by a high-output state rather than elevated pulmonary vascular resistance: a prospective 3-dimensional echocardiography/Doppler study. PloS One, 10, 2015, e0135472.
72. 72 Audard, V., Homs, S., Habibi, A., et al. Acute kidney injury in sickle patients with painful crisis or acute chest syndrome and its relation to pulmonary hypertension. Nephrol Dial Transplant 25 (2010), 2524–2529.
73. 73 Sharpe, C.C., Thein, S.L., Sickle cell nephropathy - a practical approach. Br J Haematol 155 (2011), 287–297.
74. 74 Sharpe, C.C., Thein, S.L., How I treat renal complications in sickle cell disease. Blood 123 (2014), 3720–3726.
75. 75 Powars, D.R., Elliott-Mills, D.D., Chan, L., et al. Chronic renal failure in sickle cell disease: risk factors, clinical course, and mortality. Ann Intern Med 115 (1991), 614–620.
76. 76 Serjeant, G.R., Serjeant, B.E., Mason, K.P., et al. The changing face of homozygous sickle cell disease: 102 patients over 60 years. Int J Lab Hematol 31 (2009), 585–596.
77. 77 Laurin, L.P., Nachman, P.H., Desai, P.C., et al. Hydroxyurea is associated with lower prevalence of albuminuria in adults with sickle cell disease. Nephrol Dial Transplant 29 (2014), 1211–1218.
78. 78 Aygun, B., Mortier, N.A., Smeltzer, M.P., et al. Hydroxyurea treatment decreases glomerular hyperfiltration in children with sickle cell anemia. Am J Hematol 88 (2013), 116–119.
79. 79 Steinberg, M.H., Erythropoietin for anemia of renal failure in sickle cell disease. N Engl J Med 324 (1991), 1369–1370.
80. 80 Scheinman, J.I., Sickle cell disease and the kidney. Nat Clin Pract Nephrol 5 (2009), 78–88.
81. 81 Abbott, K.C., Hypolite, I.O., Agodoa, L.Y., Sickle cell nephropathy at end-stage renal disease in the United States: patient characteristics and survival. Clin Nephrol 58 (2002), 9–15.
82. 82 Berry, P.A., Cross, T.J., Thein, S.L., et al. Hepatic dysfunction in sickle cell disease: a new system of classification based on global assessment. Clin Gastroenterol Hepatol 5 (2007), 1469–1476.
83. 83 Green, T.W., Conley, C.L., Berthrong, M., The liver in sickle cell anemia. Bull Johns Hopkins Hosp 92 (1953), 99–127.
84. 84 Gardner, K., Suddle, A., Kane, P., et al. How we treat sickle hepatopathy and liver transplantation in adults. Blood 123 (2014), 2302–2307.
85. 85 Schubert, T.T., Hepatobiliary system in sickle cell disease. Gastroenterology 90 (1986), 2013–2021.
86. 86 Johnson, C.S., Omata, M., Tong, M.J., et al. Liver involvement in sickle cell disease. Medicine 64 (1985), 349–356.
87. 87 Ebert, E.C., Nagar, M., Hagspiel, K.D., Gastrointestinal and hepatic complications of sickle cell disease. Clin Gastroenterol Hepatol 8 (2010), 483–489.
88. 88 Leikin, S.L., Gallagher, D., Kinney, T.R., et al. Mortality in children and adolescents with sickle cell disease. Cooperative Study of Sickle Cell Disease. Pediatrics 84 (1989), 500–508.
89. 89 Ohene-Frempong, K., Weiner, S.J., Sleeper, L.A., et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood 91 (1998), 288–294.
90. 90 Strouse, J.J., Jordan, L.C., Lanzkron, S., et al. The excess burden of stroke in hospitalized adults with sickle cell disease. Am J Hematol 84 (2009), 548–552.
91. 91 Adams, R.J., McKie, V.C., Hsu, L., et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial doppler ultrasonography. N Engl J Med 339 (1998), 5–11.
92. 92 Adams, R.J., TCD in sickle cell disease: an important and useful test. Pediatr Radiol 35 (2005), 229–234.
93. 93 Kassim, A.A., Galadanci, N.A., Pruthi, S., et al. How I treat and manage strokes in sickle cell disease. Blood 125 (2015), 3401–3410.
94. 94 Steen, R.G., Fineberg-Buchner, C., Hankins, G., et al. Cognitive deficits in children with sickle cell disease. J Child Neurol 20 (2005), 102–107.
95. 95 Debaun, M.R., Armstrong, F.D., McKinstry, R.C., et al. Silent cerebral infarcts: a review on a prevalent and progressive cause of neurologic injury in sickle cell anemia. Blood 119 (2012), 4587–4596.
96. 96 Mackin, R.S., Insel, P., Truran, D., et al. Neuroimaging abnormalities in adults with sickle cell anemia: associations with cognition. Neurology 82 (2014), 835–841.
97. 97 Vermeer, S.E., Prins, N.D., den Heijer, T., et al. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 348 (2003), 1215–1222.
98. 98 Anie, K.A., Psychological complications in sickle cell disease. Br J Haematol 129 (2005), 723–729.
99. 99 Puffer, E., Schatz, J., Roberts, C.W., The association of oral hydroxyurea therapy with improved cognitive functioning in sickle cell disease. Child Neuropsychol 13 (2007), 142–154.
100. 100 Ataga, K.I., Key, N.S., Hypercoagulability in sickle cell disease: new approaches to an old problem. Hematology Am Soc Hematol Educ Program, 2007, 91–96.
101. 101 Lim, M.Y., Ataga, K.I., Key, N.S., Hemostatic abnormalities in sickle cell disease. Curr Opin Hematol 20 (2013), 472–477.
102. 102 Naik, R.P., Streiff, M.B., Haywood, C. Jr., et al. Venous thromboembolism in adults with sickle cell disease: a serious and under-recognized complication. Am J Med 126 (2013), 443–449.
103. 103 Naik, R.P., Streiff, M.B., Haywood, C. Jr., et al. Venous thromboembolism incidence in the Cooperative Study of Sickle Cell Disease. J Thromb Haemost 12 (2014), 2010–2016.
104. 104 van Hamel Parsons, V., Gardner, K., Patel, R., et al. Venous thromboembolism in adults with sickle cell disease: experience of a single centre in the UK. Ann Hematol 95 (2016), 227–232.
105. 105 Charache, S., Terrin, M.L., Moore, R.D., et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med 332 (1995), 1317–1322.
106. 106 Elford, H.L., Effect of hydroxyurea on ribonucleotide reductase. Biochem Biophys Res Commun 33 (1968), 129–135.
107. 107 Bridges, K.R., Barabino, G.D., Brugnara, C., et al. A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy. Blood 88 (1996), 4701–4710.
108. 108 Benkerrou, M., Delarche, C., Brahimi, L., et al. Hydroxyurea corrects the dysregulated L-selectin expression and increased H(2)O(2) production of polymorphonuclear neutrophils from patients with sickle cell anemia. Blood 99 (2002), 2297–2303.
109. 109 Cokic, V.P., Smith, R.D., Beleslin-Cokic, B.B., et al. Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclase. J Clin Invest 111 (2003), 231–239.
110. 110 Ballas, S.K., Kesen, M.R., Goldberg, M.F., et al. Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management. ScientificWorld Journal, 2012, 2012, 949535.
111. 111 Josephson, C.D., Su, L.L., Hillyer, K.L., et al. Transfusion in the patient with sickle cell disease: a critical review of the literature and transfusion guidelines. Transfus Med Rev 21 (2007), 118–133.
112. 112 Quirolo, K., How do I transfuse patients with sickle cell disease?. Transfusion 50 (2010), 1881–1886.
113. 113 Bernaudin, F., Socie, G., Kuentz, M., et al. Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood 110 (2007), 2749–2756.
114. 114 Walters, M.C., Patience, M., Leisenring, W., et al. Stable mixed hematopoietic chimerism after bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transplant 7 (2001), 665–673.
115. 115 Gaziev, J., Lucarelli, G., Stem cell transplantation for hemoglobinopathies. Curr Opin Pediatr 15 (2003), 24–31.
116. 116 Hsieh, M.M., Fitzhugh, C.D., Weitzel, R.P., et al. Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell transplantation for severe sickle cell phenotype. JAMA 312 (2014), 48–56.
117. 117 Traxler, E.A., Yao, Y., Wang, Y.D., et al. A genome-editing strategy to treat beta-hemoglobinopathies that recapitulates a mutation associated with a benign genetic condition. Nat Med 22 (2016), 987–990.
118. 118 Hoban, M.D., Orkin, S.H., Bauer, D.E., Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease. Blood 127 (2016), 839–848.
119. 119 Mansilla-Soto, J., Riviere, I., Sadelain, M., Genetic strategies for the treatment of sickle cell anaemia. Br J Haematol 154 (2011), 715–727.
120. 120 Pleasants, S., Epidemiology: a moving target. Nature 515 (2014), S2–S3.